SKAP1 explained

Src kinase-associated phosphoprotein 1 is an adapter protein that in humans is encoded by the SKAP1 gene.^{[1] [2]}

This gene encodes a T cell adapter protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a PH domain and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adapter protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins.

The demonstration that SKAP1 regulates LFA-1 adhesion was made by retroviral infection ^[3] and by the SKAP1 deficient mouse.^[4] Additional work has implicated SKAP1 in binding to the exchange factor RasGRP1 and in regulating ERK activation in T-cells.^{[5] [6]}

Interactions

SKAP1 has been shown to interact with FYN,^{[7] [8]} PTPRC^[9] and FYB.^{[8] [10]}

Further reading

• Schraven B, Marie-Cardine A, Koretzky G . Molecular analysis of the fyn-complex: cloning of SKAP55 and SLAP-130, two novel adaptor proteins which associate with fyn and may participate in the regulation of T cell receptor-mediated signaling . Immunology Letters . 57 . 1–3 . 165–9 . June 1997 . 9232446 . 10.1016/S0165-2478(97)00053-9 .
• Clements JL, Boerth NJ, Lee JR, Koretzky GA . Integration of T cell receptor-dependent signaling pathways by adapter proteins . Annual Review of Immunology . 17 . 89–108 . 1999 . 10358754 . 10.1146/annurev.immunol.17.1.89 .
• Liu J, Kang H, Raab M, da Silva AJ, Kraeft SK, Rudd CE . FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells . Proceedings of the National Academy of Sciences of the United States of America . 95 . 15 . 8779–84 . July 1998 . 9671755 . 21153 . 10.1073/pnas.95.15.8779 . 1998PNAS...95.8779L . free .
• Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ, Zhao H, Schraven B, Koretzky GA . Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130 . The Journal of Biological Chemistry . 273 . 40 . 25789–95 . October 1998 . 9748251 . 10.1074/jbc.273.40.25789 . free .
• Kouroku Y, Soyama A, Fujita E, Urase K, Tsukahara T, Momoi T . RA70 is a src kinase-associated protein expressed ubiquitously . Biochemical and Biophysical Research Communications . 252 . 3 . 738–42 . November 1998 . 9837776 . 10.1006/bbrc.1998.9637 .
• Kang H, Freund C, Duke-Cohan JS, Musacchio A, Wagner G, Rudd CE . SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55 . The EMBO Journal . 19 . 12 . 2889–99 . June 2000 . 10856234 . 203341 . 10.1093/emboj/19.12.2889 .
• Wu L, Fu J, Shen SH . SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription . Molecular and Cellular Biology . 22 . 8 . 2673–86 . April 2002 . 11909961 . 133720 . 10.1128/MCB.22.8.2673-2686.2002 .
• Wu L, Yu Z, Shen SH . SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation . The Journal of Biological Chemistry . 277 . 43 . 40420–7 . October 2002 . 12171928 . 10.1074/jbc.M206023200 . free .
• Huang Y, Norton DD, Precht P, Martindale JL, Burkhardt JK, Wange RL . Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells . The Journal of Biological Chemistry . 280 . 25 . 23576–83 . June 2005 . 15849195 . 10.1074/jbc.M413201200 . free .
• Jo EK, Wang H, Rudd CE . An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R . The Journal of Experimental Medicine . 201 . 11 . 1733–9 . June 2005 . 15939789 . 2213273 . 10.1084/jem.20042577 .
• Duke-Cohan JS, Kang H, Liu H, Rudd CE . Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein . The Journal of Biological Chemistry . 281 . 19 . 13743–50 . May 2006 . 16461356 . 10.1074/jbc.M508774200 . free .
• Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, Freund C, Kasirer-Friede A, Menasche G, Koretzky GA, Schraven B . The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1 . Molecular and Cellular Biology . 26 . 19 . 7130–44 . October 2006 . 16980616 . 1592884 . 10.1128/MCB.00331-06 .

Notes and References

1. Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B . Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes . The Journal of Biological Chemistry . 272 . 26 . 16077–80 . June 1997 . 9195899 . 10.1074/jbc.272.26.16077 . free .
2. Web site: Entrez Gene: SKAP1 src kinase associated phosphoprotein 1.
3. Wang H, Moon EY, Azouz A, Wu X, Smith A, Schneider H, Hogg N, Rudd CE . SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates . Nature Immunology . 4 . 4 . 366–74 . April 2003 . 12652296 . 10.1038/ni913 . 11810379 .
4. Wang H, Liu H, Lu Y, Lovatt M, Wei, B, Rudd CE Functional defects of SKAP-55 deficient T-cells identify a regulatory role for the adaptor in LFA-1 adhesion, Mol. Cell. Biol. 2007 27, 6863-75.
5. • Kosco KA, Cerignoli F, Williams S, Abraham RT, Mustelin T . SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1 . Molecular Immunology . 45 . 2 . 510–22 . January 2008 . 17658605 . 10.1016/j.molimm.2007.05.024 .
6. Schneider H., Wang H., Raab M., Valk E., Smith X., Lovatt M., Wu Z., Strebhardt K, Rudd, CE. Adaptor SKAP55 binds RasGRP1 and negatively regulates p21ras and the ERK pathway in T-cells. (2008) PLoS ONE. 3, 1718.
7. Wu L, Yu Z, Shen SH . SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation . The Journal of Biological Chemistry . 277 . 43 . 40420–7 . October 2002 . 12171928 . 10.1074/jbc.M206023200 . free .
8. Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ, Zhao H, Schraven B, Koretzky GA . Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130 . The Journal of Biological Chemistry . 273 . 40 . 25789–95 . October 1998 . 9748251 . 10.1074/jbc.273.40.25789 . free .
9. Wu L, Fu J, Shen SH . SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription . Molecular and Cellular Biology . 22 . 8 . 2673–86 . April 2002 . 11909961 . 133720 . 10.1128/MCB.22.8.2673-2686.2002 .
10. Liu J, Kang H, Raab M, da Silva AJ, Kraeft SK, Rudd CE . FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells . Proceedings of the National Academy of Sciences of the United States of America . 95 . 15 . 8779–84 . July 1998 . 9671755 . 21153 . 10.1073/pnas.95.15.8779 . 1998PNAS...95.8779L . free .